Monoclonal antibodies (mAb) show an important therapeutic utility in the treatment of a wide variety of diseases such as infectious diseases, cardiovascular disease, inflammation, and cancer. (Storch (1998) Pediatrics 102:648-651; Coller et al. (1995) Thromb. Haemostasis 74:302-308; Present et al. (1999) New Eng. J. Med. 6:1398-1405; Goldenberg (1999) Clin. Ther. 21:309-318). Cells produce antibodies in response to infection or immunization with a foreign substance or antigen. The potential therapeutic utility of monoclonal antibodies is in part due to their specific and high-affinity binding to a target. Antibodies bind specifically to a target antigen by recognizing a particular site, or epitope, on the antigen. With the use of the recently developed XenoMouse® technology (Abgenix, Inc., Fremont, Calif.) together with established procedures for hybridoma cells or B cells (Kohler and Milstein (1975) Nature 256:495-497) and isolating lymphocytes (Babcook et al. (1996) Proc. Natl. Acad. Sci. 93:7843-7848), it is possible to generate large numbers of antigen-specific human monoclonal antibodies against almost any human antigen. (Green (1999) Jnl. Immunol. Methods 231:11-23, Jakobovits et al. (1993) Proc. Natl. Acad. Sci. U.S.A., 90:2551-2555, Mendez et. al. (1997) Nat. Genet. 15:146-156; Green and Jakobivits, J. Exp. Med. (1998), 188:483-495).
The large numbers of antibodies generated against a particular target antigen may vary substantially in terms of both how strongly they bind to the antigen as well as the particular epitope they bind to on the target antigen. Different antibodies generated against an antigen recognize different epitopes and have varying binding affinities to each epitope. In order to identify therapeutically useful antibodies from the large number of generated candidate antibodies, it is necessary to screen large numbers of antibodies for their binding affinities and epitope recognition properties. For this reason, it would be advantageous to have a rapid method of screening antibodies generated against a particular target antigen to identify those antibodies that are most likely to have a therapeutic effect. In addition, it would be advantageous to provide a mechanism for categorizing the generated antibodies according to their target epitope binding sites.